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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline study with acceptable restrictions (partly limited documentation, only 0.05 mL applied).
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study is comparable to OECD Guideline 404 with acceptable restrictions (partly limited documentation, e.g. no scoring 48 h after exposure; ca. 1 mL test substance applied, exposure period 20 h and occlusive coverage conditions [worst case scenario]).
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Skin irritation was tested using an internal method (BASF test) which is similar to OECD 404.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material: dimethylacetamide (DMAC)
- Purity: 99.9 %
No further details available.
Species:
rabbit
Strain:
Vienna White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2.35 kg (male), 2.63 kg (female)

No further details available.
Type of coverage:
occlusive
Preparation of test site:
other: no data (presumably shaved)
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: approximately 1 mL

The application site (dorsal skin) was covered with a cotton patch of 2.5 x 2.5 cm; the patch was soaked with the test substance and applied to the skin; no further data.
Duration of treatment / exposure:
1, 5, or 15 minutes (washing with Lutrol or 50 % aqueous Lutrol) or 20 h (unwashed)
Observation period:
Results were recorded each working day for up to 7 days (exceptions: see Table 2). The first scoring was conducted 24 h after initiation.
Number of animals:
2 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: After the reported exposure time the skin was washed (not after 20 h exposure).

SCORING SYSTEM:
BASF grading for redness and edema (see Table 1 below).
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 2 animals
Time point:
other: 24-96 h
Score:
1
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: 20 h exposure period; no edema detected; fine scaling in one rabbit at day 7
Irritant / corrosive response data:
In the female rabbit no effects were detected after 1-15 minutes exposure except a slight reddening on the day of exposure, and concerning 15 minutes exposure a slight reddening also at the day after exposure; in the male rabbit also no effects were detected except a questionable reddening 1-3 days after exposure for 1-15 minutes.

Data after 20 h exposure are presented in the Table 2 below.
No edema was seen in any test animal. At all time points for scoring not more than a questionable reddening was detected, which was reversible after 7 days. One rabbit showed a fine scaling 7 days after application.
Other effects:
Body weight was not altered in both animals.
No further effects were reported.

Table 2: Skin erythema in 2 rabbits after dermal exposure to the undiluted test substance for 20 h

Time after initiation of exposure

20 hours exposure; erythema in

Rabbit 1 (f)

Rabbit 2 (m)

24 h

1

1

48 h

no data

no data

72 h

1

1

4 days

1

1

 7 days  fine scales  0

- Evaluation transformed to OECD-Draize scoring; no edema reported.

Interpretation of results:
GHS criteria not met
Conclusions:
DMAC was no skin irritant in rabbit. A slight transient (questionable) reddening of the skin was noted.
Executive summary:

In a study according to a BASF internal standard method comparable to OECD 404, two rabbits were dermally exposed to undiluted liquid test substance (ca. 1 mL) for 1, 5, 15 minutes or for 20 h to the back skin. The coverage was occlusive; the skin was washed after exposure (not after the exposure period of 20 h). Skin reaction was scored 24, 72, 96 h and 7 days after initiation.

The test substance had only slight skin irritant properties after an exposure period of 20 h. Questionable to slight reddening was found after 1-15 minutes of exposure, effects were reversible 48-96 h after exposure. After the 20 h exposure period no edema was seen in any test animal. At all time points for scoring not more than a questionable reddening (OECD score 1) was detected, which was reversible after 7 days. One rabbit showed a fine scaling 7 days after application. Therefore, the test substance was considered to be no skin irritant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1970
Report Date:
1970

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Eye irritation was tested using an internal method (BASF test) similar to OECD405.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material: dimethylacetamide (DMAC)
- Purity: 99.9 %
No further details available.

Test animals / tissue source

Species:
rabbit
Strain:
Vienna White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Body weight: 2.66 kg (male), 2.12 kg (female)

No further details available.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: 1 drop of physiological saline was instilled into the other eye.
Amount / concentration applied:
TEST MATERIAL
- Amount applied:1 drop (corresponding to appr. 50 mm³)
Duration of treatment / exposure:
No washing
Observation period (in vivo):
10 minutes, 1, 3, 24, 48, 72 hours, 6, 8 days after instillation
Number of animals or in vitro replicates:
2 rabbits
Details on study design:
No washing of the test substance after 24 h (compare with OECD Guideline 405).

SCORING SYSTEM: BASF scores. Scoring was converted to OECD Guideline 405 grading (see table 1).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 10 minutes, 1, 3, 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: other time points score 0
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 3 & 24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Remarks on result:
other: other time points score 1
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 3, 24, 48, 72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: score 1 after 6 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: all time points up to day 6
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Remarks on result:
other: score 1 after 8 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: other time points score 1
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 8days
Remarks on result:
other: other time points score 1; still score 1 at termination
Irritant / corrosive response data:
No effects in control eye. Other effects: see Table1 below. The reddening reached max. score 2 in both rabbits and was not completely reversible in one rabbit after 8 days (score 1); chemosis reached also score 2 but was not evident for 24 h (related to observation period >= 24 h after application). Corneal opacity reached score 2 only for one time point (24 h, both rabbits), later evaluation resulted in score 1; the effects were not completely reversible in one rabbit after 8 days. However, effects were regressive with time in both rabbits.
Other effects:
There were no other effects.

Any other information on results incl. tables

Table 1: Eye irritation in rabbits after instillation of 0.05 mL undiluted test substance

Rabbit 1 (male) // Rabbit 2 (female)

Time after application

Erythema

Chemosis

Opacity of the cornea

Iritis

Remark

10 min

2//2

2//1

0//0

0//0

Increased secretion in rabbit 1 and 2

1 h

1//2

2//1

1//1

0//0

Increased secretion in rabbit 1 and 2

3 h

2//2

2//2

1//1

0//0

-

24 h

2//2

2//2

2//2

0//0

-

48 h

2//2

0//1

1//1

1//0

Bleeding of the mucous membrane in rabbit 2

72 h

2//2

0//1

1//1

0//0

Bleeding of the mucous membrane in rabbit 2

6 days

1//2

0//0

0//1

0//0

Bleeding of the mucous membrane in rabbit 2

8 days

0//1

0//0

0//1

0//0

-

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
DMAC was irritating to the rabbit eye.
Executive summary:

Two Vienna White rabbits received instillation of one drop (approx. 50 mm³) of the undiluted test substance into the conjunctival sac. The other eye was treated with physiological saline for control. Scoring was performed 10 minutes, 1, 3, 24, 48, 72 hours and 6 and 8 days after instillation. The reddening reached max. score 2 in both rabbits and was not completely reversible in one rabbit after 8 days (score 1); chemosis reached also score 2 but was not evident for 24 h (related to observation period >= 24 h after application). Corneal opacity reached score 2 only for one time point (24 h, both rabbits), later evaluation resulted in score 1; the effects were not completely reversible in one rabbit after 8 days. However, effects were regressive with time in both rabbits.

In conclusion, undiluted test substance was irritant to the rabbit eye.